DESCRIPTION (Verbatim from the Applicant's Abstract): Two recent randomized prospective studies, including a study at the British Columbia (BC) Cancer Agency, have shown that adjuvant irradiation of the chest wall and nodal beds draining the breast improves survival, even in patients with as few as 1-3 axillary Iymph node metastases. Although this approach included treatment to the internal mammary nodal (IMN) chain, the importance of IMN irradiation is unknown, and the inclusion of IMN radiotherapy in post-surgical radiotherapy remain controversial. This is due to the fact that (1) only a subset of patients who are candidates for adjuvant nodal bed radiotherapy actually have IMN metastases and (2) IMN radiotherapy carries potential cardiac, lung, and mediastinal toxicity. Current clinical practice does not include IMN biopsy, in part due to the morbidity of undirected IMN sampling. FDG PET is a non-invasive imaging method with high sensitivity for axillary lymph node metastases. Our preliminary studies suggest that it is highly accurate in detecting IMN metastases as well. Our recent work has also shown that lymphatic mapping with peri-lesional injection and lymphoscintigraphy can determine which tumors drain to the IMN. We hypothesize that a stepwise approach to IMN metastasis diagnosis using FDG PET to identify macrometastases and lymphoscintigraphy to identify drainage to the IMN can select patients for IMN biopsy and radiotherapy. Once validated this approach would rationally select patients for IMN radiation therapy and would require IMN biopsy in only a subset of patients. We propose a diagnostic study which will be a joint project between University of Washington and the BC Cancer Agency as an extension of an established collaboration. In this study we will (1) develop the role of FDG PET and lymphoscintigraphy in identifying IMN metastases, (2) identify tumor features that predict a higher risk for IMN metastases, and (3) develop methods for using FDG PET to help plan radiotherapy. This diagnostic study will provide important data to direct future internal mammary radiotherapy trials.